The effects of moderate neonatal ethanol exposure on eyeblink conditioning and deep cerebellar nuclei neuron numbers in the rat

Abstract

Heavy, bingelike patterns of exposure to ethanol during a portion of the early postnatal period in the rat, a time of rodent brain development corresponding to the human third trimester, has been shown to deplete cerebellar neurons and to produce deficits in cerebellar-dependent tasks. In the current study, we examined the impact of more moderate ethanol exposure, during an extended portion of the rat third trimester equivalent, on cerebellar-dependent learning (eyeblink conditioning) and deep cerebellar nuclei neuron numbers. Neonatal rats received 0, 1, 2, or 3 g/kg/day of ethanol in milk formula via a single intragastric intubation each day across postnatal days 2–11, or were left untreated. Peak BACs for ethanol-exposed rats were 50, 150, and 225 mg/dl, respectively. Rats underwent eyeblink conditioning as young adults (70 days of age) and deep cerebellar nuclei neuron numbers were assessed at 100 days of age. In Experiment 1, all rats showed normal responsiveness to periorbital stimulation prior to conditioning. The 3-g/kg/day group was impaired in eyeblink conditioning and possessed fewer deep cerebellar nuclei neurons. A trend toward impairment was observed in the 2-g/kg/day group. However, the 0-g/kg/day group was also impaired in eyeblink conditioning. In Experiment 2, the unconditioned stimulus pretest phase was eliminated, the 0-g/kg/day group learned normally, and both the 2- and 3-g/kg/day groups were again impaired. These results suggest that more moderate doses of ethanol during the rat third-trimester equivalent can produce long-term effects on the cerebellum.